Sulfanilic acid catalysed one-pot three-component Mannich reaction for synthesis of β-amino ketones

Cite this paper: Vietnam J. Chem., 2020, 58(5), 675-687 Article DOI: 10.1002/vjch.202000090 675 Wiley Online Library © 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH Sulfanilic acid catalysed one-pot three-component Mannich reaction for synthesis of β-amino ketones Pramod Kulkarni Department of Chemistry, Hutatma Rajguru Mahavidyalaya, Rajgurunagar, Pune-410505, MS India Submitted June 1, 2020; Accepted August 18, 2020 Abstract We have reported sulfanilic acid as an exceedingly competent catalyst for one-pot Mannich reaction to give β- amino carbonyl compounds in good to excellent yield within a short reaction time. The various organic acids have screened; like gallic acid, 4-hydroxy benzoic acid, 4-amino benzoic acid, phenylacetic acid, chloroacetic acid, sulfosalicylic acid, sulfanilic acid, chloro benzoic acid, phthalic acid, salicylic acid, cinnamic acid, hippuric acid, 1- naphthyl acetic acid, o-amino benzoic acid, p-TSA, succinic acid, malic acid, and among them sulfanilic acid is a suitable catalyst. The reaction condition was optimized with respect to the solvent, the amount of catalyst as well as the variation of the ketone, aldehyde, and amine substrates. The procedure is mild, effective, ecofriendly, and the use of the minimum amount of catalyst. Keywords. Aldehydes, amino ketone, organic acid, multicomponent, Mannich reaction. 1. INTRODUCTION Multicomponent reaction is unique important reactions in organic synthesis. These reactions in the last two decades have acknowledged the consideration of organic chemists because of various merits over conventional traditional synthesis. Multicomponent reactions have significant applications in medicinal chemistry for the creation of diverse scaffolds and combinatorial libraries for drug development. [1] In the multicomponent reactions, three or more components have been reacted to form preferably one product, which has been containing the crucial units of all the original materials. MCRs have been good for the environment by decreasing the number of synthetic steps, energy consumption, and waste creation. Therefore, the discovery of novel MCRs and elaborating on the formerly known MCRs are substantial attention. Individual example of, this type is the preparation of β-amino carbonyl compounds by the Mannich reaction. Several β- amino ketones and their analogues, show the effective medicinal properties [2-13] are shown in figure 1. β-amino ketones, have vital intermediates in the preparation of various nitrogen-containing natural products, and pharmaceutically important compounds. [14] It is evidence that the reaction comprises two equilibrating constituents (imine formation and enol tautomerization) and therefore, demands harsh reaction conditions. Due to this, it is afflicted by some severe weaknesses, namely complex work-up, and purification procedures, and unwanted side products. [15] From the first report of the Mannich reaction, numerous studies have published to improve the reaction conditions and present new and efficient catalysts for this reaction. The Mannich reactions of ketones, aldehydes, and amines have been reported through Lewis acid, [16-19] Lewis base, [20] Brønsted acids, [21-23] Metal Triflates, [24-27] and transition metal salts. [28-30] Even with the merits of these methodologies; use of transition metal compounds and heavy metal compounds as the catalyst, preparation of the catalyst, problems recycling and reusing of the catalysts, toxic reagents, and solvents, drastic reaction conditions, toxicity, or difficulty in product separation has persisted disquiets. Hence, the exploration of the newfangled green method has stagnant being keenly pursued. On the other hand, because of growing concerns about environmental effects; execution of organic reactions using organocatalyst has extremely needed in recent years. Apart from being environmentally friendly, organocatalyst has obeyed green chemistry principle like casings mild conditions, consequently saving energy, oxygen-stable reagents and does not require anhydrous conditions, reducing the cost of the synthesis, less toxic and safer substances, stop the creation of metallic waste and avoids traces of Vietnam Journal of Chemistry Pramod Kulkarni © 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 676 metals in the products. [31] Here, we have used Sulfanilic acid as organocatalyst in a one-pot three- component Mannich reaction for the synthesis of β- amino ketone. Figure 1: Medicinal properties of β-amino ketone Sulfanilic acid is valuable, low-cost, and eco- friendly, and occurs as a grayish-white powder, which is stable and incompatible with strong oxidizing agents. The literature survey reveals that it has been applied as a catalyst for the synthesis of a variety of heterocyclic compounds. [32-39] The sulfanilic acid that occurs in solid form is present as a zwitterion. Sulfonic acid groups (-SO3H) can be deprotonated to become negative sulfonate (-SO3 - ) and amino groups which can be protonated to become positive ammonium groups (-NH3 + ). The zwitterionic property of sulfanilic acid may be responsible for the excellent catalytic property in organic synthesis. Sulfanilic acid is commercially available, economical, non polluting and easy to handle, non-inflammable, and a stable catalyst related to other organoacid catalysts which are eroding, costly and afford intensely acidic conditions. [40] Here we reported the use of sulfanilic as organocatalyst in one-pot three-component Mannich reaction for the synthesis of β-amino ketone. 2. MATERIALS AND METHODS All the starting materials were got from commercially accessible sources and used without further purification. Melting points were measured by open capillary technique and are uncorrected. FTIR spectra were noted on alpha T BRUKER model. 1 H-NMR and 13 C-NMR spectra were recorded at ambient temperature on a BRUKER AVANCE DRX-500 MHz spectrophotometer using CDCl3 as the solvent and TMS as an internal standard. The purity of newly synthesized compounds and the changes of reaction were observed by thin layer chromatography (TLC) on Merck pre-coated silica gel 60 F254 aluminum sheets, visualized by UV light. General preparative procedure of β-Amino ketone: A mixture of ketone (5 mmol), substituted benzaldehyde (5mmol), substituted aniline (5mmol) and sulfanilic acid (20 mol%) in 10 mL ethanol was stirred at room temperature for the respective time specified in tables 4 and 5. The progress of the reaction was checked by TLC. Subsequent completion of the reaction, the reaction mass is poured on crushed ice. The precipitate was filtered off, and washed with cold ethanol and dried in air to get pure product. The solid product was purified by recrystallization in the ethanol and the oily product was purified by column chromatography. Spectral data of synthesized compounds 1. 2-[(3,7-dimethyl-1-(phenylamino)octa-2,6-dien- 1-yl)] cyclohexanone (table 4 Entry 3, 4c): Yield 45 %, m. p. 127-129 ºC. IRνmax cm -1 : 1567, 1630, 1702, 3362. 1 H-NMR (500 MHz, CDCl3, δ ppm): 1.73 (s, 9H), 1.78-1.125 (m, 2H), 1.91- 1.82 (m, 4H), 2.08-2.03 (m, 4H), 2.35-2.28 (m, 2H), 2.70-2.65 (m, 1H), 4.85 (br, s, 1H), 4.85- Vietnam Journal of Chemistry Sulfanilic acid catalysed one-pot three-component © 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 677 4.80 (m, 1H), 5.28-5.23 (m, 1H), 5.52-5.46 (m, 1H), 6.62-6.57 (m, 2H), 6.73-6.69 (m, 1H), 7.06- 7.01 (m, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 20.4, 22.1, 24.8, 25.0, 25.1, 25.8, 27.1, 40.4, 41.5, 48.8, 54.9, 113.1, 117.3, 123.8, 129.7, 131.6, 134.1, 135.3, 147.3, 210.8. ESI- MS (m/z): 325.24 (M + ), 326.22 (M+1) + . Anal. Calcd. for C22H31NO: C 81.18, H 9.60, and N 4.30%; found C 81.15, H 959, and N 4.24 %. 2. 2-[(3-hydroxy-4-methoxyphenyl) (phenylamino) methyl)] cyclohexanone (table 4 Entry 5, 4e): Yield 84 %, m. p. 157 ºC. IRνmax cm -1 : 1278, 1704, 3308; 1 H-NMR (500 MHz, CDCl3, δ ppm): 1.70-1.65 (m, 2H), 1.92-1.81 (m, 4H), 2.40-2.34 (m, 2H), 2.66-2.63 (m, 1H), 3.87 (s, 3H), 4.76 (br, s, 1H), 4.73-4.67 (m, 1H), 6.63- 6.58 (m, 2H), 6.71-6.68 (m, 1), 6.90-6.84 (m, 3H), 7.03-6.98 (m, 2H), 11.44 (s, 1H); 13 C NMR (125 MHz, CDCl3, δ ppm): 24.3, 24.9, 25.3, 41.7, 55.9, 56.2, 57.6, 113.4, 114.6, 116.5, 117.6, 121.7, 129.3, 134.8, 142.4, 147.2, 151.3, 211.2. ESI-MS (m/z): 325.17 (M + ), 326.30 (M+1) + . Anal. Calcd. for C20H23NO3: C 73.82, H 7.12, and N 4.30 %; found C 73.76, H 7.11, and N 4.26 %. 3. 2-[3-phenyl-1-(phenylamino)prop-2-en-1- yl]cyclohexanone (table 4 Entry 7, 4g): Yield 82 %, m. p. 127-128 ºC. IRνmax cm -1 : 1534, 1706, 3352; 1 H-NMR (500 MHz, CDCl3, δ ppm): 1.71-1.67 (m, 2H), 1.94-1.88 (m, 4H), 2.43-2.38 (m, 2H), 2.73-2.67 (m, 1H), 4.90 (br, s, 1H), 4.94-4.89 (m, 1H), 6.23-6.21 (dd, J = 5 Hz, 14.5 Hz, 1H), 6.50-6.45 (m, 2H), 6.57-6.54 (d, J = 14.5 Hz, 1H), 6.62-6.58 (m, 1H), 7.02-7.98 (d, J = 8.3 Hz, 2H) 7.34-7.26 (m, 5H); 13 C NMR (125 MHz, CDCl3, δ ppm): 25.5, 25.9, 26.7, 41.6, 54.1, 55.3, 113.2, 116.8, 126.7, 127.8, 128.4, 129.1, 129.8, 135.4, 135.9, 147.9, 210.9. ESI- MS (m/z) : 305.16 (M + ), 306.23 (M+1) + . Anal. Calcd. for C21H23NO: C 82.58, H 7.59, and N 4.59 %; found C 82.57, H 7.57, and N 4.56 %. 4. 2-[(5-bromo-2- hydroxyphenyl)(phenylamino)methyl]cyclohexa none (table 4 Entry 9, 4i): Yield 76 %, m. p. 1125-177 ºC. IRνmax cm -1 : 1698, 3356, 3408; 1 H- NMR (500 MHz, CDCl3, δ ppm): 1.63-1.57 (m, 2H), 1.86-1.80 (m, 4H), 2.38-2.33 (m, 2H), 2.84- 2.81 (m, 1H), 4.34 (br, s, 1H), 4.68-4.64 (m, 1H), 6.53-6.48 (m, 2H), 6.61-6.58 (m, 1H), 6.65- 6.62 (d, J = 8.3 Hz 1H), 7.06-7.02 (m, 2H), 7.13-7.08 (dd, J = 8.3 Hz, 2.4 Hz, 1H), 7.19- 7.15 (d, J = 2.4 Hz, 1H), 11.32 (s, 1H); 13 C NMR (125 MHz, CDCl3, δ ppm): 24.2, 24.8, 25.6, 41.6, 55.6, 56.9, 113.8, 115.3, 118.2, 118.9, 129.9, 130.3, 130.8, 134.6, 147.3, 153.6, 211.3. ESI-MS (m/z): 373.07 (M + ), 374.11 (M+1) + . Anal. Calcd. for C19H20BrNO2: C 60.97, H 5.39, Br 21.35 and N 3.74 %; found C 60.95, H 5.38, Br 21.34 and N 3.73 %. 5. 2-[(3-hydroxyphenyl) (phenylamino) methyl]cyclohexanone (table 4 Entry 10, 4j): Yield 80 %, m.p. 171-172 ºC. IRνmax cm -1 : 1695, 3340, 3414; 1 H-NMR (500 MHz, CDCl3, δ ppm): 1.60-1.55 (m, 2H), 1.83-1.78 (m, 4H), 2.32-2.28 (m, 2H), 2.77-2.73 (m, 1H), 4.18 (br, s, 1H), 4.56-4.53 (m, 1H), 6.45-6.40 (m, 2H), 6.54-6.51 (m, 1H), 6.62-6.59 (m, 1H), 6.66-6.63 (m, 1H), 6.70-6.67 (m, 1H), 7.06-7.02 (m, 3H), 11.56(s, 1H); 13 C NMR (125 MHz, CDCl3, δ ppm): 23.7, 24.5, 25.2, 40.9, 56.2, 57.4, 112.7, 113.2, 113.7, 116.8, 120.4, 128.4, 130.7, 141.5, 146.9, 158.1, 211.7. ESI-MS (m/z): 295.16 (M + ), 296.11 (M+1) + . Anal. Calcd. for C19H21NO2: C 77.26, H 7.17 and N 4.74 %; found C 77.25, H 7.14 and N 4.73 %. 6. 3-(anthracen-9-yl)-1-phenyl-3- (phenylamino)propan-1-one (table 5 Entry 1, 8a): Yield 76 %, m.p. 212 ºC. IRνmax cm -1 : 1692, 3323; 1 H-NMR (500 MHz, CDCl3, δ ppm): 3.05-2.98 (d, J = 7 Hz, 2H), 4.67-4.62 (br s, 1H), 5.04-5.01 (t, J = 7 Hz, 1H), 6.43-6.39 (m, 2H), 6.52-6.49 (m, 1H), 7.01-6.98 (m, 2H), 7.32-7.28 (m, 2H), 7.38-7.35 (m, 2H), 7.44-7.41 (m, 2H), 7.48-7.45 (m, 1H), 7.54-7.51 (s, 1H), 7.64-7.61 (m, 2H), 7.76-7.72 (m, 2H), 7.93-9.90 (m, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 51.3, 73.6, 112.8, 117.6, 124.8, 125.7, 126.3, 126.8, 127.3, 127.9, 128.2, 128.8, 128.9, 129.4, 129.6, 130.3, 133.4, 134.2, 136.4, 137.5, 147.8, 200.4. ESI- MS (m/z): 401.19 (M + ), 402. 22 (M+1) + . Anal. Calcd. for C29H23NO: C 86.125, H 5.77 and N 3.49%; found C 86.74, H 5.76 and N 3.45%. 7. 3-(2,5-dimethoxyphenyl)-1-phenyl-3- (phenylamino)propan-1-one (table 5 Entry 3, 8c): Yield 82 %, m.p. 212 ºC. IRνmax cm -1 : 1265, 1340, 1634, 1684, 3393; 1 H-NMR (500 MHz, CDCl3, δ ppm): 3.14-3.10 (d, J = 6.8 Hz, 2H), 3.84 (s, 3H), 3.91 (s, 3H), 4.55-4.51 (br s, 1H), 4.96-4.93 (t, J = 7 Hz, 1H), 6.43-6.39 (m, 2H), 6.63-6.45 (m, 5H), 7.07-7.04 (s, 1H), 7.18-7.12 (m, 2H), 7.56-7.42 (m, 3H), 7.88-7.83 (m, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 47.5, 55.6, 55.8, 74.1, 111.8, 112.5, 114.3, 115.4, 117.9, 128.6, 129.1, 132.0, 133.5, 136.7, 147.1, 147.8, 148.1, 151.2, 154.2, 200.2. ESI-MS (m/z): 361.17 (M + ), 362. 19 (M+1) + . Anal. Calcd. for Vietnam Journal of Chemistry Pramod Kulkarni © 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 678 C23H23NO3: C 76.43, H 6.41 and N 3.88 %; found C 76.37, H 6.38 and N 3.87 %. 8. 3-(4-nitrophenylamino-3-(4-methoxyphenyl)-1- phenylpropan-1-one (table 5 Entry 6, 8f): Yield 82 %, m.p. 137-139 ºC. IRνmax cm -1 : 1238, 1367, 1424, 1457, 1611, 1687, 3368; 1 H-NMR (500 MHz, CDCl3, δ ppm): 3.34-3.34 (d, J = 6.4 Hz, 2H), 3.92 (s, 3H), 4.80-4.125 (br s, 1H), 5.17- 5.12 (t, J = 6.4 Hz, 1H), 6.72-6.67 (d, J = 8.2 Hz, 2H), 6.80-6.77 (d, J = 7.8 Hz, 2H), 7.04- 6.97 (d, J = 7.8 Hz, 2H), 7.38-7.34 (m, 2H), 7.47-7.43 (m, 1H), 7.84-7.80 (m, 2H), 8.04-7.99 (d, J = 8.2 Hz, 2H); 13 C-NMR (125 MHz, CDCl3, δ ppm): 50.3, 55.6, 72.5, 114.3, 114.8, 121.5, 127.8, 128.3, 128.8, 133.5, 135.7, 136.6, 153.5, 158.9, 200.3. ESI-MS (m/z): 376.14 (M + ), 377.16 (M+1) + . Anal. Calcd. for C22H20N2O4: C 70.20, H 5.36, and N 7.44 %; found C 70.19, H 5.36, and N 7.46 %. 9. 3-(2-mercaptophenylamino)-3-(3- hydroxyphenyl)-1-phenylpropan-1-one (table 5 Entry 7, 8g): Yield 70 %, m.p. 118 ºC. IRνmax cm -1 : 1243, 1373, 1428, 1443, 1620, 1682, 2569, 3359; 1 H-NMR (500 MHz, CDCl3, δ ppm): 3.23-3.17 (d, J = 7.6 Hz, 2H), 4.04 (s, -SH, 1H), 4.76-4.72 (br s, 1H), 5.06-4.99 (t, J = 7.6 Hz, 1H), 6.30-6.27 (m, 1H), 6.43-6.38 (m, 1H), 6.56-6.48 (m, 2H), 6.65-6.62 (m, 1H), 6.84-6.81 (m, 1H), 6.94-6.91 (m, 1H), 7.06-7.03 (m, 1H), 7.32-7.28 (m, 2H), 7.42-7.39 (m, 1H), 7.86-7.81 (m, 2H), 11.87 (s, 1H); 13 C NMR (125 MHz, CDCl3, δ ppm): 52.4, 71.7, 112.4, 113.2, 113.8, 116.5, 117.6, 119.2, 125.2, 128.3, 128.9, 130.7, 133.1, 136.9, 144.3, 144.9, 158.5, 200.1. ESI- MS (m/z): 349.11 (M + ), 350.15 (M+1) + . Anal. Calcd. for C21H19NO2S: C 72.18, H 5.48, N 4.01 and S 9.18 %; found C 72.17, H 5.42, N 3.99 and S 9.17 %. 10. 3-(2-chlorophenylamino)-3-(3-hydroxyphenyl)- 1-phenylpropan-1-one (table 5 Entry 8, 8h): Yield 73 %, m.p. 108 ºC. IRνmax cm -1 1437, 1614, 1678, 3367; 1 H-NMR (500 MHz, CDCl3, δ ppm): 3.27-3.24 (d, J = 6.9 Hz, 2H), 4.68-4.64 (br s, 1H), 4.97-4.92 (t, J = 6.9 Hz, 1H), 6.33- 6.30 (m, 1H), 6.47-6.43 (m, 1H), 6.60-6.53 (m, 2H), 6.68-6.64 (m, 1H), 6.88-6.84 (m, 1H), 6.96- 6.93 (m, 1H), 7.09-7.04 (m, 1H), 7.35-7.32 (m, 2H), 7.44-7.41 (m, 1H), 7.89-7.85 (m, 2H), 11.70(s, 1H); 13 C NMR (125 MHz, CDCl3, δ ppm): 52.8, 71.9, 112.8, 113.6, 113.9, 118.4, 119.5, 122.8, 125.7, 128.4, 129.6, 130.4, 133.4, 137.6, 144.6, 145.4, 157.6, 200.6. ESI-MS (m/z): 351.11 (M + ), 352.12 (M+1) + . Anal. Calcd. for C21H18ClNO2: C 71.69, H 5.16, Cl 10.8 and N 3.98 %; found C 71.64, H 5.15, Cl 10.7 and N 3.97. 11. 3-(benzo[d]thiazol-2-ylamino)-3-(4- bromophenyl)-1-phenylpropan-1-one (table 5 Entry 9, 8i): Yield 40 %, m.p. 145-147 ºC. IRνmax cm -1 1456, 1625, 1674, 3354; 1 H-NMR (500 MHz, CDCl3, δ ppm): 3.06-2.99 (d, J = 7.2 Hz, 2H), 4.84-4.80 (br s, 1H), 5.04-4.97 (t, J = 7.2 Hz, 1H), 7.06-7.03 (d, J = 8.4, 2H), 7.30- 7.26 (m, 2H), 7.42-7.40 (d, J = 8.4, 2H), 7.48- 7.45 (m, 1H), 7.60-7.56 (m, 2H), 7.93-7.90 (m, 2H), 8.14-8.10 (m, 1H), 8.28-8.21 (m, 1H); 13 C NMR (125 MHz, CDCl3, δ ppm): 53.4, 72.6, 121.6, 122.2, 122.7, 124.8, 125.8, 126.3, 128.4, 129.1, 131.9, 133.7, 136.2, 142.3, 149.1, 174.6, 200.2. ESI-MS (m/z): 437.42 (M + ), 438.46 (M+1) + . Anal. Calcd. for C22H17BrN2OS: C 60.42, H 3.92, Br 18.27, N 6.41 and S 7.33 %; found C 60.43, H 3.90, Br 18.24, N 6.40 and S 7.32 %. 12. 3-(4-(trifluoromethyl)phenylamino)-1,5- diphenylpent-4-en-1-one (table 5 Entry 10, 8j): Yield 33 %, m.p. 140-142 ºC. IRνmax cm -1 1630, 1683, 3373; 1 H-NMR (500 MHz, CDCl3, δ ppm): 2.83-2.68 (d, J = 7.2 Hz, 2H), 3.78-3.68 (dt, J = 7.2 Hz, 6.4 Hz, 1H), 4.20-4.12 (br s, 1H), 6.16-6.12 (dd, J = 15.3 Hz, 6.4 Hz, 1H), 6.32-6.28 (d, J = 8.3 Hz, 2H), 6.45-6.42 (d, J = 15.3 Hz, 1H), 7.10-7.05 (m, 1H), 7.18-7.14 (m, 2H), 7.29-7.25 (d, J = 8.3 Hz, 2H), 7.52-7.38 (m, 5H), 7.88-7.81 (m, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 51.2, 53.6, 113.4, 119.8, 124.1, 126.6, 127.1, 128.4, 128.7, 128.8, 129.3, 133.6, 135.7, 137.1, 151.2, 200.9. ESI-MS (m/z): 395.12 (M + ), 396.17 (M+1) + . Anal. Calcd. for C24H20F3NO: C 72.90, H 5.10, F 14.41 and N 3.54 %; found C 72.87, H 5.09, F 14.39 and N 3.52. 13. 3-(4H-1,2,4-triazol-4-ylamino)-1,5- diphenylpent-4-en-1-one (table 5 Entry 11, 8k): Yield 2 %, m.p. 109-111 ºC. IRνmax cm -1 1610, 1645, 1688, 3356; 1 H-NMR (500 MHz, CDCl3, δ ppm): 2.78-2.61 (d, J = 7.6 Hz, 2H), 3.72-3.60 (dt, J = 7.6 Hz, 6.9 Hz, 1H), 4.15-4.05 (br s, 1H), 6.20-6.15 (dd, J = 15.9 Hz, 6.9 Hz, 1H), 6.49-6.45 (d, J = 15.9 Hz, 1H), 7.33-7.12 (m, 5H), 7.48-7.37 (m, 3H), 7.89-7.85 (m, 2H), 8.22- 8.18 (s, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 49.2, 51.1, 126.6, 127.7, 128.2, 128.5, 128.8, 129.3, 129.6, 133.4, 135.9, 137.0, 144.6, 200.3. ESI-MS (m/z): 318.20 (M + ), 319.21 (M+1) + . Anal. Calcd. for C19H18N4O: C 71.68, Vietnam Journal of Chemistry Sulfanilic acid catalysed one-pot three-component © 2020 Vietnam Academy of Science and Technology, Hanoi & Wiley-VCH GmbH www.vjc.wiley-vch.de 679 H 5.70, and N 17.60 %; found C 71.67, H 5.66, and N 17.58. 14. 3-(4-fluorophenylamino)-1,5-diphenylpent-4-en- 1-one (table 5 Entry 12, 8l): Yield 82 %, m. p. 126-128 ºC. IRνmax cm -1 1623, 1679, 3368; 1 H- NMR (500 MHz, CDCl3, δ ppm): 2.80-2.65 (d, J = 7.5 Hz, 2H), 3.72-3.60 (dt, J = 7.5 Hz, 6.9 Hz, 1H), 4.73-4.65 (br s, 1H), 6.21-6.17 (dd, J = 15.6 Hz, 6.9 Hz, 1H), 6.37-6.33 (d, J = 7.9 Hz, 2H), 6.48-6.44 (d, J = 15.6 Hz, 1H), 6.85-6.81 (d, J = 7.9 Hz, 2H), 7.36-7.21 (m, 5H), 7.56- 7.41 (m, 3H), 7.86-7.81 (m, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 50.7, 53.3, 115.3, 116.7, 126.9, 127.8, 128.1, 128.5, 128.8, 128.9, 129.7, 133.3, 135.1, 136.6, 144.3, 151.6, 200.5. ESI- MS (m/z): 345.17 (M + ), 346.18 (M+1) + . Anal. Calcd. for C23H20FNO: C 79.98, H 5.84, F 5.50 and N 4.06 %; found C 79.97, H 5.49, F 5.52 and N 4.05 %. 15. 3-(1-phenylethylamino)-1,5-diphenylpent-4-en- 1-one (table 5 Entry 13, 8m): Yield 78 %, m. p. 134-137 ºC. IRνmax cm -1 1612, 1676, 3338; 1 H- NMR (500 MHz, CDCl3, δ ppm): 1.27-1.22 (d, J = 6.8Hz, 3H), 2.74-2.68 (d, J = 7.8 Hz, 2H), 3.69-3.54 (dt, J = 7.8 Hz, 6.2 Hz, 1H), 4.55-4.43 (br s, 1H), 4.87-4.83 (q, J = 6.8 Hz, 1H), 6.15- 6.12 (dd, J = 15.1 Hz, 6.2 Hz, 1H), 6.43-6.38 (d, J = 15.1 Hz, 1H), 7.27-7.05 (m, 10H), 7.53-7.41 (m, 3H), 7.91-7.88 (m, 2H); 13 C NMR (125 MHz, CDCl3, δ ppm): 21.4, 47.3, 51.4, 55.5, 126.1, 127.4, 127.6, 128.2, 128.4, 128.7, 128.9, 129.0, 129.3, 129.6, 133.4, 135.1, 136.8, 137.9, 138.2, 200.1. ESI-MS (m/z): 355.20 (M + ), 356.23 (M+1) + . Anal. Calcd. for C25H25NO: C 84.47, H 7.09, and N 3.94 %; found C 84.49, H 7.08, and N 3.93 %. 16. 3-(2-chlorophenylamino-3-(anthracen-9-yl)-1- phenylpropan-1-one (table 5 Entry 14, 8n): Yield 62 %, m.p. 181-184 ºC. IRνmax cm -1 1634, 1683, 3361; 1 H-NMR (500 MHz, CDCl3, δ ppm)